Blood coagulation-related parameter changes in Sprague-Dawley (SD) rats treated with phenobarbital (PB) and PB plus vitamin K

Mochizuki, Masahiro; Shimizu, S.; Kitazawa, Takahiro; Umeshita, Kazuhiko; Goto, Ken; Kamata, Takashi; Aoki, Ayumi; Hatayama, Kazumi

doi:10.2131/jts.33.307

Cited by 7 publications

(7 citation statements)

References 18 publications

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“…botest ® was employed as it specifically measures the activities of vitamin K-dependent coagulation factors II, VII, IX and X. It is a comprehensive indicator for the activity of factors II, VII, IX and X including an effect of proteins induced by vitamin K absence or antagonism-II (PIVKA-II), which inhibits coagulation factors, and is used as a monitoring assay for the diagnosis of vitamin K previous study (Mochizuki et al, 2008). Bouwman et al (1999) reported that administration of HxCB, to germfree casein diet resulted in CYP2B induction, increase of vitamin K 2,3-epoxide reductase activity and decrease of factor VII.…”

Section: Discussionmentioning

confidence: 99%

“…However, there are no reports of effects of PB-administration to dams on the coagulation system of newborn pups in laboratory animals. Recently we reported that prolongation of coagulation time and increased ATIII concentration were observed in SpragueDawley rats which were treated with PB (Mochizuki et al, 2008). There are almost no reports of the effects of PB on coagulation time in rabbits which are widely used for toxicological studies.…”

Section: Introductionmentioning

confidence: 99%

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Changes in blood coagulation-related parameters in phenobarbital-treated rabbits

et al. 2009

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-The effects of repeated administration of phenobarbital (PB) on blood coagulation time were examined using male Japanese white SPF rabbits, which are widely used for toxicological studies. PB was administered to the rabbits by oral gavage for 2 weeks, at dose levels of 0, 12.5, 25 and 50 mg/kg/ day. Blood was collected on Days 8 and 14 after each day's dosing to perform blood coagulation examination. The liver was excised, weighed and examined histopathologically. Activated partial thromboplastin time (APTT) was prolonged at dose levels of 12.5 mg/kg/day or more and Thrombotest ® (TBT) was prolonged at 50 mg/kg/day on Day 8. APTT was prolonged at dose levels of 12.5 mg/kg/day or more, TBT was prolonged at 25 mg/kg/day or more and factor IX activity decreased at 50 mg/kg/day on Day 14. At pathological examination, liver weight increased at dose levels of 25 mg/kg/day or more, and a groundglass appearance of the hepatocytes was observed in the central and middle parts of lobules at 12.5 mg/ kg/day or more. However, changes in factor VII or X activity or prolongation of prothrombin time (PT) were not observed. Therefore, prolongation of blood coagulation time by PB administration in rabbits was considered to be due to PB's effect on the endogenous pathway alone. Moreover, an increase in antithrombin III (ATIII) concentration was noted at 50 mg/kg/day; however, no change was noted at dose levels of 25 mg/kg/day or less. This suggests that the contribution of ATIII to the PB-induced prolongation of coagulation time in rabbits was small.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Changes in blood coagulation-related parameters in phenobarbital-treated rabbits

et al. 2009

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“…This suggests that a vitamin in non-pregnant and pregnant rats. We recently reported that prolongation of APTT was observed from Day 1 of repeated administration of PB to male rats (Mochizuki et al, 2008). Prolongation of blood coagulation time by single administration of HxCB was more severe in males than that in females (Bouwman et al, 1999).…”

Section: Discussionmentioning

confidence: 93%

“…Recently we reported that prolongation of blood coagulation time was observed in both male Sprague-Dawley rats and male Japanese white rabbits which were treated with PB (Mochizuki et al, 2008). However, there are almost no reports of effects of PB on blood coagulation time in pregnant or lactating dams and their pups, although they are widely used in reproduction studies.…”

Section: Introductionmentioning

confidence: 99%

Phenobarbital (PB)-induced changes in blood coagulationrelated parameters in pregnant rats, lactating rats and pups

et al. 2009

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-Effects of repeated administration of phenobarbital (PB) on blood coagulation-related parameters were examined in non-pregnant, pregnant and lactating rats, and also in pups born to PB-treated lactating dams. PB was orally administered at a dose level of 80 mg/kg/day to pregnant (from gestation day (GD) 13), postpartum (from postpartum day (PPD) 7) and non-pregnant rats (from 13 weeks of age) for 7 days. Blood was collected on GD20 or PPD14 to perform blood coagulation examination. Concurrently, the blood coagulation parameters were examined in the pups. Increases in liver weight and/or hepatic cytochrome P450 content were observed in the PB-treated non-pregnant, pregnant and lactating rats. Activated partial thromboplastin time (APTT) was prolonged and anti-thrombin III (ATIII) concentration was increased in the lactating rats, while there were no changes in prothrombin time (PT) or APTT in the non-pregnant and pregnant rats. Moreover, prolongation of PT and APTT and decreases in factors VII and IX activities were observed in their pups. Thus, prolongation of blood coagulation time was con-2 (VK 2 ) on PB-induced changes in blood coagulation-related parameters of both dams and their pups were examined by co-administration with PB and VK 2 to lactating dams. PT and APTT were comparable to the control and PB-induced prolongation of blood coagulation time was improved in the pups while APTT was prolonged in dams, suggesting that VK 2

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“…Initial validation experiments using microwell fluorescence assays suggested significant and semi-selective antiproliferative activity of MQ on Jurkat cells relative to noncancerous lymphoblasts 8 . MQ’s primary physiological role and mechanism in blood coagulation is well-studied and well-understood 9–11 . Previous studies have shown that MQ can in fact have antiproliferative effects in certain cancer cell types: it can trigger both apoptotic and autophagic programmed cell death, as well as both intrinsic and extrinsic pathways of apoptosis, in a variety of cell types including colon cancer 12 , acute myeloid leukemia 13 , hepatocellular carcinoma 14, 15 , prostate cancer 16 , and cervical carcinoma 17 .…”

Section: Introductionmentioning

confidence: 99%

Metabolomics identifies the intersection of phosphoethanolamine with menaquinone-triggered apoptosis in an in vitro model of leukemia

et al. 2015

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Altered metabolism is increasingly acknowledged as an important aspect of cancer, and thus serves as a potentially fertile area for the identification of therapeutic targets or leads. Our recent work using transcriptional data to predict metabolite levels in cancer cells led to preliminary evidence of the antiproliferative role of menaquinone (Vitamin K2) in the Jurkat cell line model of acute lymphoblastic leukemia. However, nothing is known about the direct metabolic impacts of menaquinone in cancer, which could provide insights into its mechanism of action. Here, we used metabolomics to investigate the process by which menaquinone exerts antiproliferative activity on Jurkat cells. We first validated the dose-dependent, semi-selective, pro-apoptotic activity of menaquinone treatment on Jurkat cells relative to non-cancerous lymphoblasts. We then used mass spectrometry-based metabolomics to identify systems-scale changes in metabolic dynamics that are distinct from changes induced in non-cancerous cells or by other chemotherapeutics. One of the most significantly affected metabolites was phosphoethanolamine, which exhibited a two-fold increase in menaquinone-treated Jurkat cells compared to vehicle-treated cells at 24 h, growing to a five-fold increase at 72 h. Phosphoethanolamine elevation was observed prior to the induction of apoptosis, and was not observed in menaquinone-treated lymphoblasts or chemotherapeutic-treated Jurkat cells. We also validated the link between menaquinone and phosphoethanolamine in an ovarian cancer cell line, suggesting potentially broad applicability of their relationship. This metabolomics-based work is the first detailed characterization of the metabolic impacts of menaquinone treatment and the first identified link between phosphoethanolamine and menaquinone-induced apoptosis.

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Blood coagulation-related parameter changes in Sprague-Dawley (SD) rats treated with phenobarbital (PB) and PB plus vitamin K

Cited by 7 publications

References 18 publications

Changes in blood coagulation-related parameters in phenobarbital-treated rabbits

Changes in blood coagulation-related parameters in phenobarbital-treated rabbits

Phenobarbital (PB)-induced changes in blood coagulationrelated parameters in pregnant rats, lactating rats and pups

Metabolomics identifies the intersection of phosphoethanolamine with menaquinone-triggered apoptosis in an in vitro model of leukemia

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